Mmp12, also known as macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation [3]. It has been implicated in various biological processes and disease conditions, with genetic models being valuable for studying its functions.

In a mouse model of silicosis, macrophage-derived MMP12 was shown to promote fibrosis through sustained damage to endothelial cells, with MMP12 accumulating on the extracellular matrix and mediating endothelial cell dysfunction during different phases of the disease [1]. In a mouse model of subretinal fibrosis, MMP12 critically contributed to the development of the condition, partially through promoting macrophage-to-myofibroblast transition (MMT) [2]. In ApcMin/+ mice (a model of colorectal cancer), MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area, preventing weight and muscle loss associated with cancer cachexia [4]. Also, in a mouse model mimicking human cardiometabolic diseases, genetic deletion of MMP12 ameliorated obesity-induced low-grade inflammation, white adipose tissue dysfunction, and the development of atherosclerosis [5]. In corneal injury models, MMP12 was found to inhibit corneal inflammation and neovascularization after injury through its regulation of CCL2 [6].

In conclusion, Mmp12 is a key factor involved in ECM degradation and has diverse functions in diseases such as fibrosis, subretinal fibrosis, cancer cachexia, and cardiometabolic diseases. Gene knockout mouse models have been instrumental in revealing its role in these specific disease areas, providing insights into potential therapeutic strategies targeting Mmp12 [1,2,4,5,6].